title: Highway proximity associated with cardiovascular disease risk: the influence of individual-level confounders and exposure misclassification.
abstract: BACKGROUND
  Elevated cardiovascular disease risk has been reported with proximity to highways or busy roadways, but proximity measures can be challenging to interpret given potential confounders and exposure error.
  
  
  METHODS
  We conducted a cross sectional analysis of plasma levels of C-Reactive Protein (hsCRP), Interleukin-6 (IL-6), Tumor Necrosis Factor alpha receptor II (TNF-RII) and fibrinogen with distance of residence to a highway in and around Boston, Massachusetts. Distance was assigned using ortho-photo corrected parcel matching, as well as less precise approaches such as simple parcel matching and geocoding addresses to street networks. We used a combined random and convenience sample of 260 adults >40 years old. We screened a large number of individual-level variables including some infrequently collected for assessment of highway proximity, and included a subset in our final regression models. We monitored ultrafine particle (UFP) levels in the study areas to help interpret proximity measures.
  
  
  RESULTS
  Using the orthophoto corrected geocoding, in a fully adjusted model, hsCRP and IL-6 differed by distance category relative to urban background: 43% (-16%,141%) and 49% (6%,110%) increase for 0-50 m; 7% (-39%,45%) and 41% (6%,86%) for 50-150 m; 54% (-2%,142%) and 18% (-11%,57%) for 150-250 m, and 49% (-4%, 131%) and 42% (6%, 89%) for 250-450 m. There was little evidence for association for TNF-RII or fibrinogen. Ortho-photo corrected geocoding resulted in stronger associations than traditional methods which introduced differential misclassification. Restricted analysis found the effect of proximity on biomarkers was mostly downwind from the highway or upwind where there was considerable local street traffic, consistent with patterns of monitored UFP levels.
  
  
  CONCLUSIONS
  We found associations between highway proximity and both hsCRP and IL-6, with non-monotonic patterns explained partly by individual-level factors and differences between proximity and UFP concentrations. Our analyses emphasize the importance of controlling for the risk of differential exposure misclassification from geocoding error.
authors.affiliation: Tufts University School of Medicine, Boston, MA, USA. dbrugge@aol.com.
authors.forename: Doug
authors.initials: D
authors.lastname: Brugge
authors.forename: Kevin
authors.initials: K
authors.lastname: Lane
authors.forename: Luz T
authors.initials: LT
authors.lastname: Padró-Martínez
authors.forename: Andrea
authors.initials: A
authors.lastname: Stewart
authors.forename: Kyle
authors.initials: K
authors.lastname: Hoesterey
authors.forename: David
authors.initials: D
authors.lastname: Weiss
authors.forename: Ding Ding
authors.initials: DD
authors.lastname: Wang
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Levy
authors.forename: Allison P
authors.initials: AP
authors.lastname: Patton
authors.forename: Wig
authors.initials: W
authors.lastname: Zamore
authors.forename: Mkaya
authors.initials: M
authors.lastname: Mwamburi
mesh_terms: D000328:Adult; D000368:Aged; D000393:Air Pollutants / Q000097:blood* / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D001900:Boston / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology*; D003430:Cross-Sectional Studies; D004781:Environmental Exposure; D004784:Environmental Monitoring; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*; D012111:Residence Characteristics; D012307:Risk Factors; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter; D001335:Vehicle Emissions